Sedation-free transnasal esophagoscopy to evaluate and monitor esophageal diseases in children with esophageal atresia-tracheoesophageal fistula.

Patients with esophageal atresia and tracheoesophageal fistula (EA-TEF) are at increased risk of conditions including gastroesophageal reflux, peptic esophagitis, gastric metaplasia, anastomotic strictures, eosinophilic esophagitis, and dysphagia. Patients with TEF-EA may need serial endoscopy in their lifetime given the known short- and long-term GI complications. There has been increased interest in pediatric unsedated transnasal endoscopy (TNE) as an endoscopic alternative as it is lower cost, has shorter recovery time, and eliminates potential risks associated with anesthesia. We report on the use of TNE with EA-TEF in four patients: One patient had gastroesophageal reflux disease, one patient had eosinophilic esophagitis and TNE was used for surveillance in two patients. Use of TNE allowed for close endoscopic monitoring and changes in medication management. The third and fourth patients underwent TNE as part of routine EA-TEF screening which is recommended by societal guidelines (Krishnan et al, J Pediatr Gastroenterol Nutr. 2016;63(5):550-570). Unsedated TNE is an alternative endoscopic approach in the management of patients with EA-TEF.

The Gut Microbiota Differ in Exclusively Breastfed and Formula-Fed United States Infants and are Associated with Growth Status.

BACKGROUND: Evidence regarding the effects of infant feeding type (exclusive breastfeeding compared with exclusive formula feeding) on the gut microbiota and how it impacts infant growth status is limited. OBJECTIVES: The primary objective was to compare gut microbiota by feeding type and characterize the associations between gut microbiota and infant growth status. METHODS: Stool samples from healthy, full-term infants (4-5 mo-old) who were either exclusively breastfed (BF) or exclusively formula-fed (FF) in Denver, CO, United States were collected, and fecal 16S ribosomal ribonucleic acid gene-based profiling was conducted. Length and weight were measured at the time of stool collection. Length-for-age z-score, weight-for-age z-scores (WAZ), and weight-for-length z-scores were calculated based on the World Health Organization standards. Associations between gut microbial taxa and anthropometric z-scores were assessed by Spearman's rank correlation test. RESULTS: A total of 115 infants (BF n = 54; FF n = 61) were included in this study. Feeding type (BF compared with FF) was the most significant tested variable on gut microbiota composition (P < 1 × 10-6), followed by mode of delivery and race. Significant differences were observed in α-diversity, ß-diversity, and relative abundances of individual taxa between BF and FF. BF infants had lower α-diversity than FF infants. Abundances of Bifidobacterium and Lactobacillus were greater in the breastfeeding group. FF infants had a higher relative abundance of unclassified Ruminococcaceae (P < 0.001), which was associated with a higher WAZ (P < 0.001) and length-for-age z-score (P < 0.01). Lactobacillus was inversely associated with WAZ (P < 0.05). CONCLUSIONS: Feeding type is the main driver of gut microbiota differences in young infants. The gut microbiota differences based on feeding type (exclusive breast- or formula feeding) were associated with observed differences in growth status. This trial was registered at clinicaltrials.gov as NCT02142647, NCT01693406, and NCT04137445.

In Esophageal Squamous Cells From Eosinophilic Esophagitis Patients, Th2 Cytokines Increase Eotaxin-3 Secretion Through Effects on Intracellular Calcium and a Non-Gastric Proton Pump.

BACKGROUND & AIMS: In upper airway cells, T helper 2 cytokines that signal through interleukin-4 (IL-4) receptor-α have been shown to stimulate eotaxin-3 secretion via a nongastric proton pump (ngH+,K+ATPase). To seek novel targets for eosinophilic esophagitis (EoE) treatments, we evaluated ngH+,K+ATPase expression in EoE squamous cells, and explored molecular pathways involved in eotaxin-3 secretion by IL-4 receptor-α signaling. METHODS: ngH+,K+ATPase expression in EoE cells was evaluated by quantitative real-time polymerase chain reaction and Western blotting. IL-4-stimulated eotaxin-3 secretion was measured by enzyme-linked immunosorbent assay after treatment with omeprazole, SCH 28080 (potassium-competitive acid blocker), ethylene glycol-bis(ß-aminoethyl)-N,N,N',N'-tetraacetoxymethyl ester (calcium chelator), 2-aminoethoxydiphenyl borate (inhibitor of endoplasmic reticulum calcium release), verapamil, and diltiazem (L-type calcium channel inhibitors). Intracellular calcium transients were measured by Fluo-4 fluorescence. Key experiments were confirmed in EoE primary cells and in RNA sequencing datasets from mucosal biopsies of patients with EoE and controls. RESULTS: EoE cells expressed ngH+,K+ATPase messenger RNA and protein. Omeprazole and SCH 28080 decreased IL-4-stimulated eotaxin-3 secretion. IL-4 increased intracellular calcium transients, and IL-4-stimulated eotaxin-3 secretion was blocked by ethylene glycol-bis(ß-aminoethyl)-N,N,N',N'-tetraacetoxymethyl ester, 2-aminoethoxydiphenyl borate, verapamil, and diltiazem. The combination of omeprazole and verapamil suppressed IL-4-stimulated eotaxin-3 secretion more than either agent alone. EoE biopsies expressed higher ngH+,K+ATPase and exhibited more calcium signaling than controls. CONCLUSIONS: EoE cells express a nongastric proton pump that mediates T helper 2 cytokine-stimulated eotaxin-3 secretion. IL-4 induces calcium release from the endoplasmic reticulum and calcium entry via L-type calcium channels, increasing intracellular calcium that contributes to eotaxin-3 secretion by EoE cells. L-type calcium channel inhibitors block T helper 2 cytokine-stimulated eotaxin-3 secretion, suggesting a potential role for these agents in EoE treatment.

Utility of MRIs in adult cochlear implant evaluations.

OBJECTIVES: To determine the prevalence of MRI abnormalities in adults undergoing cochlear implantation and to correlate abnormalities to audiology data. STUDY DESIGN: Case series. SETTING: Academic medical center. METHODS: Adult patients (>18 yr old) undergoing cochlear implant evaluation from January 2008 to December 2012 were identified based on CPT code search. Demographics, preoperative MRI findings, operative findings, and audiometric data were collected. RESULTS: The study included 188 patients. Seventeen (9%) patients had significant otic capsule or vestibulocochlear nerve pathologies: 5 vestibular schwannomas, 4 enlarged vestibular aqueducts, 2 hypoplastic cochlear nerves, 2 labyrinthitis ossificans, 1 cochlear aplasia, 1 posterior semicircular canal malformation, 1 calcified meningioma, and 1 cholesterol granuloma. MRI results were normal (65%) or with findings not directly related to hearing loss (incidental findings, 25%) in the remaining patients. Mean pure tone average (PTA) differences (between the implanted and contralateral ear) did not significantly vary between normal-incidental and abnormal MRI scans (-6.6 dB versus -6.7 dB, p = 0.99) nor did speech discrimination scores (SDS) scores (8.5% versus 8.4%, p = 0.99). No significant difference was found in HINT scores for patients with a normal versus an abnormal MRI (19% versus 16,%, p = 0.62). CONCLUSION: Although the majority of precochlear implantation MRIs were normal or demonstrated incidental findings, such as white matter changes, significant MRI findings affecting implantation site and patient counseling were found in almost 10% of patients. Audiogram findings did not correlate with abnormal findings on MRIs. Routine use of MRI in adult cochlear implant candidates may be warranted.